{"title":"Plasma Cell Crystalline Inclusions in ALK-Negative Anaplastic Large Cell Lymphoma","authors":"Hiromi Kinoshita, Tsugumi Satoh, Hidekazu Kayano, Naoki Takahashi, Yasuhiro Ebihara","doi":"10.1002/jha2.70080","DOIUrl":null,"url":null,"abstract":"<p>A 79-year-old woman presented with hematochezia. Endoscopic examination revealed a polyp in the rectum, and endoscopic mucosal resection was performed. The pathological diagnosis was carcinoma in adenoma, pTis (M). No further treatment was performed for this tumor. At that time, worsened hepatic dysfunction and fever were noted. A computed tomography scan showed systemic lymph nodes swelling and hepatosplenomegaly, indicating malignant lymphoma. Laboratory data showed markedly elevated soluble interleukin-2 receptor and lactate dehydrogenase levels of 48,897 U/mL (reference value: 204–587) and 3699 U/L (reference value: 124–222), respectively, which supported the diagnosis of lymphoma. Immunoglobulin levels were not elevated.</p><p>Bone marrow showed aggregations of abnormal lymphoid cells (Figure 1a), which possessed distinct nucleoli, abundant cytoplasm, and moderate to large irregularly shaped nuclei (Figure 1b). These cells were positive for CD30 (Figure 1c) and CD4 (Figure 1d), and negative for PAX-5, CD20, CD2, CD3, CD5, and CD7. Anaplastic lymphoma kinase (ALK) and Epstein–Barr virus-encoded small RNA in situ hybridization were negative. Light chain restriction was not detected by flow cytometry. Finally, a diagnosis of ALK-negative anaplastic large cell lymphoma (ALCL; clinical Stage 4) was made.</p><p>In addition to ALCL cell infiltration in bone marrow, plasma cells with crystalline inclusions, which exhibited a relatively larger, rectangular or rhomboid morphology, were found (Figure 2a–c; arrows), although the number of plasma cells were not increased (2.2%). These cells were positive for CD138 (Figure 2d), and these crystalline inclusions were negative for kappa and lambda immunoglobulins.</p><p>ALCL is a malignancy of mature T lymphocytes with expression of CD30. In a previous review of synchronous solid tumor and lymphoma, most cases involved the combination of adenocarcinoma and B-cell lymphoid lymphoma. ALCL occurring simultaneously with solid tumor is extremely rare, but there is one reported case of ductal breast carcinoma and breast-implant-associated ALCL. The relationship between rectal carcinoma in adenoma and the onset of ALCL in the present case is unknown. ALCL cells and plasma cells with inclusions were not detected in the polyp samples from the rectum of this patient.</p><p>Intracytoplasmic inclusions are occasionally seen in plasmacytoid or B-cell lymphoproliferative disorders such as multiple myeloma, but are rarely found in other diseases.</p><p>Some reports have described the detection of plasma cells around ALCL cells, but plasma cells with inclusions were not noted. The mechanism by which intracytoplasmic crystalline inclusions are produced is not well understood, but is related to the abnormal accumulation of cytoplasmic immunoglobulins secondary to disruption of the protein synthesis pathway.</p><p>In the present case, the patient's general condition was poor, so aggressive treatment for ALCL was not possible, and prednisolone was administered to treat ALCL and control inflammation. However, PSL alone was not sufficient and this situation might have exacerbated the inflammation. A cytokine storm might be triggered in response, possibly leading to increased release of inflammatory cytokines such as IL-6. As a result, immunoglobin synthesis might have been accelerated in some reactive clones of plasma cells, and cytoplasmic immunoglobulins might have abnormally accumulated.</p><p>Although the presence of plasma cells with crystalline inclusion might be coincidental, the accumulation of these reactive cases with crystalline inclusions in plasma cells may bring new insight in their relationship.</p><p>H.K. and Y.E. took the photographs and wrote the manuscript. T.S. and H.K. supported histopathological diagnosis. N.T. provided patient care. All the authors critically reviewed and approved the manuscript.</p><p>The authors have confirmed ethical approval statement is not required for this submission.</p><p>The authors declare no conflicts of interest.</p><p>The authors have confirmed that a patient consent statement is not required for this submission, as no patient-identifying data were used.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70080","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJHaem","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jha2.70080","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
A 79-year-old woman presented with hematochezia. Endoscopic examination revealed a polyp in the rectum, and endoscopic mucosal resection was performed. The pathological diagnosis was carcinoma in adenoma, pTis (M). No further treatment was performed for this tumor. At that time, worsened hepatic dysfunction and fever were noted. A computed tomography scan showed systemic lymph nodes swelling and hepatosplenomegaly, indicating malignant lymphoma. Laboratory data showed markedly elevated soluble interleukin-2 receptor and lactate dehydrogenase levels of 48,897 U/mL (reference value: 204–587) and 3699 U/L (reference value: 124–222), respectively, which supported the diagnosis of lymphoma. Immunoglobulin levels were not elevated.
Bone marrow showed aggregations of abnormal lymphoid cells (Figure 1a), which possessed distinct nucleoli, abundant cytoplasm, and moderate to large irregularly shaped nuclei (Figure 1b). These cells were positive for CD30 (Figure 1c) and CD4 (Figure 1d), and negative for PAX-5, CD20, CD2, CD3, CD5, and CD7. Anaplastic lymphoma kinase (ALK) and Epstein–Barr virus-encoded small RNA in situ hybridization were negative. Light chain restriction was not detected by flow cytometry. Finally, a diagnosis of ALK-negative anaplastic large cell lymphoma (ALCL; clinical Stage 4) was made.
In addition to ALCL cell infiltration in bone marrow, plasma cells with crystalline inclusions, which exhibited a relatively larger, rectangular or rhomboid morphology, were found (Figure 2a–c; arrows), although the number of plasma cells were not increased (2.2%). These cells were positive for CD138 (Figure 2d), and these crystalline inclusions were negative for kappa and lambda immunoglobulins.
ALCL is a malignancy of mature T lymphocytes with expression of CD30. In a previous review of synchronous solid tumor and lymphoma, most cases involved the combination of adenocarcinoma and B-cell lymphoid lymphoma. ALCL occurring simultaneously with solid tumor is extremely rare, but there is one reported case of ductal breast carcinoma and breast-implant-associated ALCL. The relationship between rectal carcinoma in adenoma and the onset of ALCL in the present case is unknown. ALCL cells and plasma cells with inclusions were not detected in the polyp samples from the rectum of this patient.
Intracytoplasmic inclusions are occasionally seen in plasmacytoid or B-cell lymphoproliferative disorders such as multiple myeloma, but are rarely found in other diseases.
Some reports have described the detection of plasma cells around ALCL cells, but plasma cells with inclusions were not noted. The mechanism by which intracytoplasmic crystalline inclusions are produced is not well understood, but is related to the abnormal accumulation of cytoplasmic immunoglobulins secondary to disruption of the protein synthesis pathway.
In the present case, the patient's general condition was poor, so aggressive treatment for ALCL was not possible, and prednisolone was administered to treat ALCL and control inflammation. However, PSL alone was not sufficient and this situation might have exacerbated the inflammation. A cytokine storm might be triggered in response, possibly leading to increased release of inflammatory cytokines such as IL-6. As a result, immunoglobin synthesis might have been accelerated in some reactive clones of plasma cells, and cytoplasmic immunoglobulins might have abnormally accumulated.
Although the presence of plasma cells with crystalline inclusion might be coincidental, the accumulation of these reactive cases with crystalline inclusions in plasma cells may bring new insight in their relationship.
H.K. and Y.E. took the photographs and wrote the manuscript. T.S. and H.K. supported histopathological diagnosis. N.T. provided patient care. All the authors critically reviewed and approved the manuscript.
The authors have confirmed ethical approval statement is not required for this submission.
The authors declare no conflicts of interest.
The authors have confirmed that a patient consent statement is not required for this submission, as no patient-identifying data were used.